Calcineurin (CaN) is a Ca2+- and calmodulin (CaM) binding protein first discovered in brain tissue in 1978 and subsequently found in many different tissue types. It is a hetero dimer composed of a large "A" subunit (60kDa) and a small "B" subunit (18kDa). CaN-A is a class 2B protein phosphatase which contains an autoinhibitory region as well as separate domains for CaN-B and CaM binding. The discovery that CaN binds to immunosuppressive drug-immunophilin complexes inplicated this enzyme as a central component of the immune response system. This proposal applies for time to collect data on heavy atom derivatives for phasing and on CaN/immunophillin-drug complexes.